4.7 Article

The characteristics of cerebrospinal fluid anaplastic large cells in a patient with primary leptomeningeal anaplastic large cell lymphoma

期刊

CLINICA CHIMICA ACTA
卷 537, 期 -, 页码 46-50

出版社

ELSEVIER
DOI: 10.1016/j.cca.2022.09.029

关键词

Cerebrospinal fluid; Primary leptomeningeal anaplastic large cell lymphoma; Single cell transcriptome

资金

  1. National Natural Science Foundation of China [82072367, 82102489, 32271165]

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This study reported a rare case of primary leptomeningeal anaplastic large cell lymphoma (PL-ALCL) and performed single-cell RNA sequencing to analyze the transcriptome characteristics of the cerebrospinal fluid anaplastic large cells (CSF-ALCs). The analysis revealed specific gene upregulation and altered transcription factor activity in CSF-ALCs, providing insight for the diagnosis and mechanism research of PL-ALCL.
Background: Primary central nervous system lymphomas (PCNSL) anaplastic large cell lymphoma (ALCL) are very rare non-Hodgkin's lymphomas, especially in the leptomeninges. Until now, the diagnostics and therapeutics of PCNSL-ALCL is a challenge and urgent need. A 26-y Chinese male presented altered awareness and severe headache. Methods: A 26-y Chinese male presented altered awareness and severe headache. Brain magnetic resonance imaging (MRI) delineated no intracerebral lesions and focal leptomeningeal enhancement. Diagnosis was based on cerebrospinal fluid (CSF) examination discovering anaplastic large cells (ALCs) with positive expression for anaplastic lymphoma kinase (ALK) and CD30, and no evidence of systemic involvement. In addition, we firstly performed the single-cell RNA sequencing to identify transcriptome characteristics of CSF-ALCs. Results: The case was diagnosed as a rare primary leptomeningeal anaplastic large cell lymphoma (PL-ALCL). Four cycles of systemic chemotherapy with methotrexate and intrathecal cytarabine help achieve complete remission. Compared to normal T cells, 45 genes were specifically upregulated in CSF-ALCs. CSF-ALCs enriched cell proliferation and metabolism pathway and lost features of immune identity. The heterogeneity of CSF-ALCs were manifested in the expression of cancer-testis antigens and cell-cycle signature genes. In addition, the gene regulatory networks (GRNs) revealed the activity of transcription factors EZH2 and NFYC were upregulated in the CSF-ALCs. Conclusion: The first analysis of single-cell transcriptome signatures of CSF-ALCs will provide clues for diagnosis and mechanism research of PL-ALCL.

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